Mild cognitive impairment (MCI) is an important condition; 10-15% of MCI subjects convert to Alzheimer's disease (AD) per year, compared to 1-2% in the general population. The long-term goal of this candidate is to develop an independent program dedicated to the prevention of AD through the investigation of risk factors for MCI. To achieve this, the candidate needs expertise and knowledge in neurodegenerative diseases, and longitudinal population-based research in MCI and AD. The candidate is applying for this K01 Mentored Research Scientist Development Award to facilitate a transition from the study of prostatic diseases to the study of neurodegenerative diseases. The K01 award will meet the long-term goal of the candidate through two short term goals: 1) To develop understanding and expertise in neurodegenerative disorders, with an emphasis on MCI, an intermediate stage between normal aging and AD; and 2) To develop expertise in identification of vascular and infammatory risk factors for MCI in a population based longitudinal cohort. These short-term goals will be accomplished through mentored activities, course work, and research. The primary mentor of this candidate, Dr. Ronald Petersen, the Principal Investigator (PI) of the population-based prospective study of MCI, and PI on a recently concluded multi-center clinical trial for MCI, will meet regularly with the candidate to discuss issues regarding characterization of MCI subjects, progress of the study, and novel research regarding MCI. In addition, the candidate will meet with secondary [unreadable] mentors in cardiovascular disease Dr Veronique Roger, an eminent cardiologist and epidemiologist with [unreadable] special interests in association of dementia and myocardial infarction; and Dr Robert Ivnik, a [unreadable] neuropsychologist with extensive experience in the development of population-based age- and educationadjusted neuropsychometric normative data for Olmsted County residents. The candidate's research plan will focus on vascular risk factors and inflammatory markers for MCI. The candidate's research plan is innovative because of the focus on non-cognitive, modifiable risk factors. While genetic risk factors may be important predictors of early onset AD, vascular risk factors may account for a larger proportion of AD. Since they are modifiable, they are more amenable to interventions that may prevent or reduce the risk of MCI and consequently, of AD. In this award, the candidate proposes to investigate hypotheses that vascular risk factors (e.g diabetes, hypertension), coronary heart disease, and inflammatory markers of vascular risk (e.g. C reactive protein) increase risk of MCI and MCI progression among participants in a longitudinal populationbased cohort. The study will be conducted at the Mayo Clinic Abigail van Buren Alzheimer's Disease Research Clinic. The K01 award will culminate in an R01 application that will pave the way for the candidate to become an independent investigator in MCI and AD research. [unreadable] [unreadable] [unreadable]